Phase II clinical trial of sorafenib plus interferon-alpha treatment for patients with metastatic renal cell carcinoma in Japan. Issue 1 (December 2015)

• Record Type: Journal Article
• Authors: Eto, Masatoshi; Kawano, Yoshiaki; Hirao, Yoshihiko; Mita, Koji; Arai, Yoichi; Tsukamoto, Taiji; Hashine, Katsuyoshi; Matsubara, Akio; Fujioka, Tomoaki; Kimura, Go; Shinohara, Nobuo; Tatsugami, Katsunori; Hinotsu, Shiro; Naito, Seiji
• Is Part Of: BMC cancer. Volume 15:Issue 1(2015)
• Page Start: 1
• Page End: 7
• Publication Date: 2015-12
• Subjects: Sorafenib -- Interferon-alpha -- Renal cell carcinoma; Cancer -- Periodicals; 616.994005
• DOI: 10.1186/s12885-015-1675-1
• Languages: English
• ISSNs: 1471-2407

Abstract

Abstract Background To improve antitumor effects against metastatic renal cell carcinoma (mRCC), use of molecular target-based drugs in sequential or combination therapy has been advocated. In combination therapy, interferon (IFN)-α amplified the effect of sorafenib in our murine model (J Urol 184:2549, 2010), and cytokine-treated mRCC patients in Japan had good prognoses (Eur Urol 57:317, 2010). We thus conducted a phase II clinical trial of sorafenib plus IFN-α for untreated mRCC patients in Japan. Methods In this multicenter, prospective study, provisionally registered patients with histologically confirmed metastatic clear cell RCC received natural IFN-α (3 dosages of 3 million U per week) for 2 weeks. Only IFN-α-tolerant patients were registered to this trial, and treated additionally with oral sorafenib (400 mg, bid). The primary end point of the study was rate of response (CR + PR) to sorafenib plus IFN-α treatment assessed using RECIST v1.0. The secondary end points were disease control rate (CR + PR + SD), progression free survival (PFS), overall survival (OS), and safety of the combined treatment. PFS and OS curves were plotted using the Kaplan-Meier method. Results From July 2009 to July 2012, a total of 53 untreated patients were provisionally registered, and 51 patients were finally registered. Rate of Response to the combined therapy of sorafenib plus IFN-α was 26.2 % (11/42) (CR 1, PR 10). The median PFS was 10.1 months (95 % CI, 6.4 to 18.5 months), and the median OS has not been reached yet. The combined therapy increased neither the incidence of adverse effects (AE) nor the incidence of unexpected AE. A limitation was that a relatively high number of patients (9 patients) were excluded for eligibility criteria violations. Conclusion Our data have demonstrated that sorafenib plus IFN-α treatment is safe and effective for untreated mRCC patients. Trial registration UMIN000002466, 9th September, 2009